http://www.klinikaikozpont.u-szeged.hu/pedia/images/pdf/CME_TEL/Full-Text/25.pdf

The Hallmarks of Aging

A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes

A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group.

The sequence of the mouse genome is a key informational tool for understanding the contents of the human genome and a key experimental tool for biomedical research. Here, we report the results of an international collaboration to produce a high-quality draft sequence of the mouse genome. We also present an initial comparative analysis of the mouse and human genomes, describing some of the insights that can be gleaned from the two sequences. We discuss topics including the analysis of the evolutionary forces shaping the size, structure and sequence of the genomes; the conservation of large-scale synteny across most of the genomes; the much lower extent of sequence orthology covering less than half of the genomes; the proportions of the genomes under selection; the number of protein-coding genes; the expansion of gene families related to reproduction and immunity; the evolution of proteins; and the identification of intraspecies polymorphism.

/pdf/initial-sequencing-and-comparative-analysis-of-the-mouse-5a9n62pifj.pdf

Initial sequencing and comparative analysis of the mouse genome.

DNA methylation is frequently described as a 'silencing' epigenetic mark, and indeed this function of 5-methylcytosine was originally proposed in the 1970s. Now, thanks to improved genome-scale mapping of methylation, we can evaluate DNA methylation in different genomic contexts: transcriptional start sites with or without CpG islands, in gene bodies, at regulatory elements and at repeat sequences. The emerging picture is that the function of DNA methylation seems to vary with context, and the relationship between DNA methylation and transcription is more nuanced than we realized at first. Improving our understanding of the functions of DNA methylation is necessary for interpreting changes in this mark that are observed in diseases such as cancer.

Functions of DNA methylation: islands, start sites, gene bodies and beyond

Publisher Summary This chapter describes the various forms of inherited lower motor neuron degeneration and discusses the current knowledge regarding the molecular basis of these disorders and the pathways underlying the specific susceptibility of motor neurons to degeneration. By convention, the use of the term “spinal muscular atrophy” (SMA) is reserved for disorders characterized by progressive muscle wasting due to the loss of motor neurons in the ventral horns of the spinal cord. The three forms of childhood onset proximal SMA—previously known as Werdnig–Hoffmann disease (type I SMA), intermediate SMA (type II), and Kugelberg–Welander syndrome (type III)—are caused by mutations in the same gene, survival of motor neurons 1 (SMN1). Supportive treatment for types I and II SMA includes respiratory assessment and nutritional support as appropriate and for type II patients corrective spinal surgery for scoliosis. Distal SMAs or hereditary motor neuronopathies (HMN) are a range of conditions characterized by slowly progressive distal wasting and weakness in the absence of clinical or electrophysiological evidence of sensory involvement. Several families have been described in which distal motor neuropathy is associated with vocal cord paralysis leading to hoarseness and stridor.

Chapter 7 Spinal muscular atrophies and hereditary motor neuropathies.

Utrophin modulation is a disease-modifying therapeutic strategy for Duchenne muscular dystrophy that would be applicable to all patient populations. To improve the suboptimal profile of ezutromid, ...

Decreasing HepG2 Cytotoxicity by Lowering the Lipophilicity of Benzo[d]oxazolephosphinate Ester Utrophin Modulators.

Genes et heredite; sondes specifiques d'un gene; analyse directe des mutations; analyse indirecte des maladies genetiques; strategies generales de cartographie des genes (RFLPs); isolement et localisation de sequences specifiques d'un chromosome; cartographie des maladies monogeniques; maladies multifactorielles

https://www.tandfonline.com/doi/pdf/10.1080/02648725.1985.10647816

The molecular genetics of human monogenic diseases.

Carriers of the fragile X mutation possess more than the normal number of copies of a trinucleotide repeat (CGG) within the coding region of a gene designated as FMR-1 in Xq27. The clinical phenotype is determined by the number of copies of the CGG repeat. DNA-based methods for the detection of the fragile X mutation are now available which greatly assist in the genetic diagnosis of this disorder. Direct detection of the mutation enables the identification of fragile X negative normal transmitting males and fragile X negative carrier females.

Kay E. Davies

Papers

Chapter 7 Spinal muscular atrophies and hereditary motor neuropathies.

Decreasing HepG2 Cytotoxicity by Lowering the Lipophilicity of Benzo[d]oxazolephosphinate Ester Utrophin Modulators.

The molecular genetics of human monogenic diseases.

Molecular analysis of the fragile X syndrome.

Molecular analysis of childhood-onset spinal muscular-atrophy